The purpose of this trial is to investigate the hypothesis that amitriptyline or desipramine (tricyclic antidepresants which have substantial noradrenergic re-uptake inhibition) have significant analgesic properties as adjuvant therapy in treating cancer patients with moderate pain that the patients feel is unacceptable despite optimized treatment with narcotics. Over the three year period, 300 patients with moderate to severe pain are being solicited for this 10 week study. The dose of the study drugs will be titrated upward over 6 weeks in the mid-range anti- depressant dose of 150 mg/day. The opiate dose will be monitored and adjusted if needed. The primary outcome measure will be a dichotomous analgesic outcome variable, which will be created from a combination of changes in each patients's daily Visual Analogue Score for pain intensity (VAS-PI) and changes in each patients opiate dose. Secondary outcome measures will include mood score (Physical/ Neurological Exam). In addition, blood samples will be drawn to evaluate if analgesia is related to anti-depressant blood levels. To determine a possible prediction model for the likely responders, the data will be reanalyzed as a cohort study. The results of this study will substantially impact on the care of cancer pain by either providing specific guidance for which groups of patients stand to benefit from this therapy.